Salubris Biotherapeutics' JK07, a novel ErbB4 agonist, has shown positive interim results in a Phase 2 clinical trial (RENEU-HF) for patients with heart failure, both with reduced (HFrEF) and preserved ejection fraction (HFpEF). The interim analysis focused on assessing the safety and tolerability of JK07 at a lower dose (0.045 mg/kg) before escalating to a higher dose (0.09 mg/kg). The data indicated a favorable safety profile, robust target engagement, and encouraging preliminary signs of efficacy. Based on these findings, the higher dose cohort has been opened for enrollment.
The RENEU-HF trial (NCT06369298) is a randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of multiple doses of JK07 in patients with HFrEF and HFpEF. The trial aims to enroll 282 subjects, randomized in a 2:1 ratio to receive either JK07 or placebo. The primary endpoint for HFrEF patients is improvement in ejection fraction, while for HFpEF patients, it is safety and tolerability.
Interim Analysis Highlights
As of the data cutoff, 68 patients had been enrolled in the trial. The interim results indicated that JK07 was safe and well-tolerated, with no significant differences in adverse event frequency or severity between the JK07 and placebo groups. Furthermore, the magnitude of target engagement was consistent throughout the first six months of the study. Preliminary efficacy data suggest trends toward improvement, although the primary endpoint analysis is scheduled for 2026.
Mechanism of Action
JK07 is a recombinant antibody fusion protein composed of an active polypeptide fragment of human neuregulin (NRG-1) and a fully human IgG1 monoclonal antibody targeting ErbB3. Neuregulin has demonstrated potential in heart failure treatment but is also associated with undesirable side effects. Research indicates that NRG-1 signals through two receptors, ErbB3 and ErbB4. The ErbB4 pathway appears to mediate the regenerative effects in the heart, while the ErbB3 pathway is linked to safety and tolerability limitations. JK07 is designed to selectively stimulate the ErbB4 pathway by blocking ErbB3 signaling, potentially widening the therapeutic window of NRG-1.
Clinical Significance
Heart failure affects an estimated 6.7 million Americans and over 64 million people globally. Both HFrEF and HFpEF impact over 3 million individuals in the US alone. Shalabh Singhal, Chief Medical Officer of SalubrisBio, stated, "We are encouraged by the safety profile and early efficacy trends from this interim analysis of RENEU-HF. The data continue to suggest that JK07 has the potential to improve function and long-term outcomes in heart failure patients."
These early findings suggest that JK07 could offer a new treatment option for improving heart function and quality of life for individuals suffering from heart failure.
